rs681561

Positions:

• chr13-100246275-A-C
• chr13-100246275-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000376285.6(PCCA):​c.637+10397A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 150,566 control chromosomes in the GnomAD database, including 23,612 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (23612 hom., cov: 32)
• Consequence: PCCA ENST00000376285.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688

Genes affected

PCCA (HGNC:8653): (propionyl-CoA carboxylase subunit alpha) The protein encoded by this gene is the alpha subunit of the heterodimeric mitochondrial enzyme Propionyl-CoA carboxylase. PCCA encodes the biotin-binding region of this enzyme. Mutations in either PCCA or PCCB (encoding the beta subunit) lead to an enzyme deficiency resulting in propionic acidemia. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCCA	NM_000282.4	c.637+10397A>C		intron_variant		ENST00000376285.6	NP_000273.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCCA	ENST00000376285.6	c.637+10397A>C		intron_variant		1	NM_000282.4	ENSP00000365462	P1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 83770 AN: 150448 Hom.: 23581 Cov.: 32

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.472

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.523

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.557 AC: 83842 AN: 150566 Hom.: 23612 Cov.: 32 AF XY: 0.560 AC XY: 41255 AN XY: 73624

Gnomad4 AFR AF: 0.636

Gnomad4 AMR AF: 0.572

Gnomad4 ASJ AF: 0.471

Gnomad4 EAS AF: 0.760

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.505

Gnomad4 NFE AF: 0.493

Gnomad4 OTH AF: 0.525

Alfa AF: 0.487 Hom.: 19835

Bravo AF: 0.557

Asia WGS AF: 0.731 AC: 2538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.67
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs681561; hg19: chr13-100898529;